New Warning For OTC Drugs Containing the Antihistamine Diphenhydramine (BENADRYL)

On December 5, 2002, the Food and Drug Administration (FDA) announced that a new warning statement would be required on the labels of all over-the-counter (OTC) antihistamine, anti-nausea, anti-cough and nighttime sleep-aid drug products containing diphenhydramine citrate or diphenhydramine hydrochloride.

The most familiar brand name for a diphenhydramine antihistamine product is BENADRYL. Some of the many products besides BENADRYL in liquid, capsule, tablet, cream and gel forms include SLEEPINAL NIGHT-TIME SLEEP AID, EXTRA STRENGTH BAYER PM ASPIRIN, some ACTIFED products, some NYTOL products, EXTRA STRENGTH DOAN’S PM, some TYLENOL products, and EXCEDRIN PM ANALGESIC SLEEPING AID, to name a few.

The new warning advises consumers not to use oral OTC diphenhydramine products with any other product also containing diphenhydramine, including products used on the skin (topically). The FDA based its decision to require the new warning on reports of diphenydramine-induced psychosis, especially in children. The agency said it was also concerned about under-reporting of adverse events because there is no current reporting requirement for topical diphenhydramine products marketed as OTC drugs.

The required warning statement for topical products will say:

Do Not Use: on chicken pox, poison ivy, sunburn, large areas of the body, broken, blistered, or oozing skin, more often than directed, or with any other product containing diphenhydramine, even one taken by mouth.

The required warning statement for oral products will say:

Do Not Use: with any other product containing diphenhydramine, even one used on skin.

The FDA also plans a similar warning on oral OTC pain relievers that contain diphenhydramine.

When diphenhydramine is applied over a wide area of the body, particularly when the skin is damaged or injured, some is absorbed into the bloodstream just as if it had been taken by mouth. Using oral and topical forms of the drug together may then cause toxic levels to build up in the bloodstream.

This has been reported in children from 19 months to nine years of age. The symptoms included dilated pupils, flushed face, hallucinations, muscular incoordination, and difficulty in urinating. These are effects that are expected from large doses of anithistamines, such as diphenhydramine, and other drugs with so-called anticholinergic adverse effects. These symptoms gradually disappeared when diphenhydramine was removed from the body by washing and discontinuing the drug by mouth.

In 1997, the FDA asked diphenhydramine producers to voluntarily add these warnings to their products because of reports of toxicity in children (see Worst Pills, Best Pills News October 1997). To the credit of a number of companies, they did voluntarily add the warnings to their products labels. What is remarkable is the fact that it has taken so long for this simple but very important safety warning to become mandatory.

What You Can Do

You should follow the advice given in the FDA required warnings for oral and topical diphenhydramine products.

Parents and consumers should always carefully read the list of ingredients on all OTC drug labels.